Upconversion nanoparticles (UCNPs) are a class of nanomaterials composed of lanthanide ions with great potential for paraclinical applications, especially in laboratory and imaging sciences. UCNPs have tunable optical properties and the ability to convert long-wavelength (low energy) excitation light into short-wavelength (high energy) emission in the ultraviolet (UV)-visible and near-infrared (NIR) spectral regions. The core-shell structure of UCNPs can be customized through chemical synthesis to meet the needs of different applications. The surface of UCNPs can also be tailored by conjugating small molecules and/or targeting ligands to achieve high specificity and selectivity, which are indispensable elements in biomedical applications. Specifically, coatings can enhance the water dispersion, biocompatibility, and efficiency of UCNPs, thereby optimizing their functionality and boosting their performance. In this context, multimodal imaging can provide more accurate in vivo information when combined with nuclear imaging. This article intends to provide a comprehensive review of the core structure, structure optimization, surface modification, and various recent applications of UCNPs in biomolecular detection, cell imaging, tumor diagnosis, and deep tissue imaging. We also present and discuss some of their critical challenges, limitations, and potential future directions.
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